Biomedical subjects

M A Mastroianni

Publications and source records attributed to M A Mastroianni.

10 recordsLinked to original sources

PubMed2006

Neuropathic and cerebrovascular correlates of hearing loss in Fabry disease.

Fabry disease, OMIM 301500, is a progressive multisystem storage disorder due to the deficiency of alpha-galactosidase A (GALA). Neurological and vascular manifestations of this disorder with regard to hearing loss have not been analysed quantitatively in large cohorts. We conducted a retrospective cross sectional analysis of hearing loss in 109 male and female patients with Fabry disease who were referred to and seen at the Clinical Center of the National Institutes of Health, Bethesda, MD, USA on natural history and enzyme replacement study protocols. There were 85 males aged 6-58 years (mean 31 years, SD 13) and 24 females aged 22-72 years (mean 42 years, SD 12). All patients underwent a comprehensive audiological evaluation. In addition, cerebral white matter lesions, peripheral neuropathy, and kidney function were quantitatively assessed. HL(95), defined as a hearing threshold above the 95th percentile for age and gender matched normal controls, was present in 56% [95% CI (42.2-67.2)] of the males. Prevalence of HL(95) was lower in the group of patients with residual GALA enzyme activity compared with those without detectable activity (33% versus 63%) HL(95) was present in the low-, mid- and high-frequency ranges for all ages. Male patients with HL(95) had a higher microvascular cerebral white matter lesion load [1.4, interquartile range (IQR) 0-30.1 +/- versus 0, IQR 0-0], more pronounced cold perception deficit [19.4 +/- 5.5 versus 13.5 +/- 5.5 of just noticeable difference (JND) units] and lower kidney function [creatinine: 1.6 +/- 1.2 versus 0.77 +/- 0.2 mg/dl; blood urea nitrogen (BUN): 20.1 +/- 14.1 versus 10.3 +/- 3.28 mg/dl] than those without HL(95) (P < 0.001). Of the females, 38% had HL(95). There was no significant association with cold perception deficit, creatinine or BUN in the females. Word recognition and acoustic reflexes analyses suggested a predominant cochlear involvement. We conclude that hearing loss involving all frequency regions significantly contributes to morbidity in patients with Fabry disease. Our quantitative analysis suggests a correlation of neuropathic and vascular damage with hearing loss in the males. Residual GALA activity appears to have a protective effect against hearing loss.

Adolescent↗

PubMed2001

Auditory dysfunction in Stickler syndrome.

OBJECTIVES: To characterize the natural history and possible mechanisms of hearing loss in Stickler syndrome (OMIM 108300; or hereditary progressive arthro-ophthalmopathy) and to determine if the auditory phenotype is a useful discriminating feature for the differential diagnosis of this group of disorders. DESIGN: Multifamily study. SETTING: Outpatient audiology and otolaryngology clinics at the Warren Grant Magnuson Clinical Center of the National Institutes of Health, Rockville, Md. SUBJECTS: Forty-six affected individuals from 29 different families segregating Stickler syndrome. INTERVENTIONS: Clinical audiologic and otolaryngological examinations were performed on all individuals, including pure-tone audiometry, speech audiometry, and middle ear immittance testing. Otoacoustic emissions, auditory brainstem response, infrared video electronystagmography, and temporal bone computed tomography were performed on a subset of participants. RESULTS: The hearing loss was most often sensorineural in adults, and approximately 28 (60%) of the 46 adult patients had 2 or more thresholds greater than the corresponding 95th percentile values for an age-matched, otologically normal population. The hearing loss most often affected high frequencies (4000-8000 Hz) and was generally no more progressive than that due to age-related hearing loss. Type A(D) tympanograms (classification using the Jerger model), indicating hypermobile middle ear systems, were observed in 21 (46%) of the 46 affected individuals. Computed tomography of the temporal bones revealed no inner ear malformations in 19 affected individuals. CONCLUSIONS: The hypermobile middle ear systems observed in ears with normal-appearing tympanic membranes represent a novel finding for Stickler syndrome and are likely to be a useful diagnostic feature for this disorder. The overall sensorineural hearing loss in type I Stickler syndrome is typically mild and not significantly progressive. It is less severe than that reported for types II and III Stickler syndrome linked to COL11A2 (OMIM 120290) and COL11A1 (OMIM 120280) mutations, respectively, or the closely related Marshall syndrome. This difference will be a useful discriminatory feature in the differential diagnosis of this group of disorders.

Adolescent↗

PubMed2000

Dominant modifier DFNM1 suppresses recessive deafness DFNB26.

More than 50% of severe childhood deafness is genetically determined, approximately 70% of which occurs without other abnormalities and is thus termed nonsyndromic. So far, 30 nonsyndromic recessive deafness loci have been mapped and the defective genes at 6 loci, DFNB1, DFNB2, DFNB3, DFNB4, DFNB9 and DNFB21, have been identified, encoding connexin-26 (ref. 3), myosin VIIA (ref. 4), myosin XV (ref. 5), pendrin, otoferlin and alpha-tectorin, respectively. Here we map a new recessive nonsyndromic deafness locus, DFNB26, to a 1.5-cM interval of chromosome 4q31 in a consanguineous Pakistani family. A maximum lod score of 8.10 at theta=0 was obtained with D4S1610 when only the 8 affected individuals in this family were included in the calculation. There are seven unaffected family members who are also homozygous for the DFNB26-linked haplotype and thus are non-penetrant. A dominant modifier, DFNM1, that suppresses deafness in the 7 nonpenetrant individuals was mapped to a 5.6-cM region on chromosome 1q24 with a lod score of 4.31 at theta=0 for D1S2815.

Chromosome Mapping↗

PubMed1998

Cochlear outer hair cell electromotility can provide force for both low and high intensity distortion product otoacoustic emissions.

It is generally believed that the force for the otoacoustic emission (OAE) generation is provided by a mechanism of electromotility, observed in isolated cochlear outer hair cells (OHCs). OHC electromotility is resistant to several ototoxic reagents, it does not depend on ATP hydrolysis, but it can be blocked by specific sulfhydryl reagents: p-chloromercuriphenylsulfonic acid (pCMPS) and p-hydroxymercuriphenylsulfonic acid (pHMPS). We have used these reagents to test whether they also affect OAE. Application of pCMPS and pHMPS on the round window membrane of anesthetized guinea pigs produced a dose-dependent inhibition of the cubic (2F1-F2) distortion product OAE (DPOAE). The inhibition developed progressively from high to low frequencies, reflecting the diffusion of the drugs through the cochlear compartment. The effect of pCMPS and pHMPS was different from the effects of furosemide and lethal anoxia, which impair cochlear function but do not block OHC electromotility. pHMPS suppressed DPOAE completely at all sound intensities tested (45-80 dB SPL), whereas furosemide or lethal anoxia caused DPOAE to disappear at low-level stimulation (45-60 dB SPL) only. Our results suggest that the OHC electromotility might provide the force for DPOAE generation not only at low, but also at high stimulus intensities.

4-Chloromercuribenzenesulfonate↗

PubMed1996

Prevalence and mechanisms of hearing loss in patients with resistance to thyroid hormone.

Hearing impairment was anecdotally reported in resistance to thyroid hormone (RTH), a condition caused by mutations in the beta-thyroid hormone receptor (beta TR) gene. Because of its ontogenic distribution in the cochlea, the beta TR may have a pivotal role in the development of auditory function. To assess the prevalence and mechanisms of hearing impairment in RTH, 82 RTH-positive (RTH+) patients and 55 unaffected relatives (RTH-) underwent systematic audiological examination, including puretone and speech reception thresholds, and tests studying middle ear (tympanometry and acoustic reflexes), cochlear (otoacoustic emissions), and retrocochlear integrity (brain stem auditory evoked potentials). Significant hearing loss was present in 21% of RTH+ patients vs. none in RTH- patients. More RTH+ patients had abnormal tympanometry (34% vs. 12%) and abnormal acoustic reflexes (39% vs. 19%). Isolated conductive deficit was found in 7 of 17 RTH+ patients with hearing loss, isolated sensorineural deficit in 7 cases, and mixed deficit in 3 cases. Cochlear dysfunction was found in 50% of all RTH+ patients, with or without hearing loss. Retrocochlear function was normal. No morphological cochlear abnormalities were detected on computed tomography of the temporal bone. In conclusion, hearing loss is a significant problem in RTH, with an equal frequency of conductive (probably related to the frequent ear infections) and sensorineural deficits. Abnormal otoacoustic emissions suggest that the mutant beta TR has a specific negative impact on cochlear function.

Adult↗

PubMed1996

beta-Endorphin and propiomelanocortin-correlates peptides response in suspected and confirmed ischemic heart disease during exercise.

UNLABELLED: In this study, we investigated circulating beta-endorphin, ACTH and cortisol in subjects with suspected coronary artery disease (CAD) and in patients with CAD during stress testing. Group I: 18 subjects, all male (average age 48 +/- 9 yrs) with suspected (CAD) were enrolled. Group II: 35 patients, 30 males and 5 females (average age 54.3 +/- 7 yrs) with CAD, were enrolled. Ten patients had previous myocardial infarction. In all patients that underwent coronarography a stenosis > 75% was found in at least one coronary artery. The stress test was performed with a cycloergometer, increasing work loads 25 watt every 2 min. All subjects and patients were in the recumbent position for at least 30 minutes prior to testing. During this period a 3-way catheter was placed in the antecubital vein and blood was drawn for Beta-endorphin, ACTH and cortisol; additional blood samples were drawn using a pre-chilled syringe at maximum effort and during the recovery period. RESULTS: group I: 9 of the subjects with suspected CAD had either ECG or clinical signs of ischemic during the stress test. In subjects with a negative test, the test was carried out for a longer period of time and at a higher work load. There was an increase in Beta-endorphin and ACTH at peak exercise and during recovery. Plasma cortisol increase during the period of recovery. Group II: 16 of the 35 patients with CAD exhibited ECG signs of induced myocardial ischemia; there was no difference in work loads in patients with positive or negative stress test. Exercise time was reduced in all patients and plasma Beta-endorphin increased at peak exercise and recovery in patients with a negative stress test. In conclusion our study revealed a different response of Beta-endorphin, ACTH and cortisol plasma levels in subjects with suspected CAD and in patients with CAD during exercise testing.

Adrenocorticotropic Hormone↗

PubMed1996

Plasma endothelin-1 concentrations in patients with coronary artery disease during stress test before and after nisoldipine administration.

The purpose of this study was to determine the response of plasma levels of endothelin-1 (ET-1) to dynamic exercise in patients with coronary artery disease and chronic stable angina pectoris and positive exercise tolerance test, before and after treatment with the calcium antagonist nisoldipine (20 mg/day buccally for 7 days). Plasma ET-1 levels and hemodynamic parameters (blood pressure and heart rate) were determined at rest, at peak exercise and recovery. All patients had a positive electrically and clinically stress test and all of the eight patients did not developed ECG signs of myocardial ischemia after nisoldipine administration. Before nisoldipine treatment the plasma ET-1 levels did not increase significantly during exercise. After nisoldipine treatment the plasma ET-1 levels were significantly lower at rest and during exercise compared with those revealed before calcium antagonist treatment. In conclusion our results suggest that in patients with chronic stable angina pectoris the treatment with calcium antagonist nisoldipine reduced ischemia and plasma ET-1 levels.

Adult↗

PubMed1995

Dynamic exercise induces elevation of plasma levels of endothelin-1 in patients with coronary artery disease.

In this investigation the response of endothelin-1 plasma levels to dynamic exercise in patients with coronary artery disease (CAD) was studied. The study population consisted of 20 patients with CAD, 16 men and 4 women (mean age 53 +/- 8.6 years). Seven normal volunteers all men (mean age 53.4 +/- 4.4 years) were studied as a control group. Seven patients had prior myocardial infarction. All patients and controls exercised on a multi-stage bicycle ergometer; plasma endothelin-1 levels and hemodynamic indices were measured at rest, at peak exercise, and at two and six minutes after exercise. Of the 20 patients examined, 7 (35%) showed electrocardiogrpahic (ECG) signs of myocardial ischemia during the stress test. The mean plasma endothelin-1 concentration increased significantly from 7.8 +/- 3.0 to 13.6 +/- 3.5 pg/mL at exercise peak (P < 0.05) only in patients who did not show ECG signs of myocardial ischemia and returned to baseline values during recovery (six minutes) (9.4 +/- 2.1 pg/mL). In normal subjects baseline endothelin-1 levels (9.4 +/- 4.2 pg/mL) were not significantly altered at peak exercise (10.8 +/- 4.7 pg/mL) and at recovery (11.3 +/- 3.6 pg/mL). The hemodynamic parameters were not correlated with the plasma endothelin-1 levels before, during, and after exercise in all groups. The present study demonstrated that the plasma levels of endothelin-1 in patients with CAD increased significantly during stress testing.

Adult↗

PubMed1994

[The effects of sublingual nifedipine on isometric stress in patients with severe aortic insufficiency. An acute hemodynamic study].

We studied the acute hemodynamic effects of nifedipine (N) on handgrip test (Hg) in 10 patients with aortic regurgitation in II NYHA functional class. In basal condition (B) we found a significant increase of mean aortic pressure (AoPmean) in all patients after Hg (101 +/- 9.72 versus 110.3 +/- 6.42 mmHg; p < 0.05). Hg did not induce significant changes of AoPmean after N. Hg increased left ventricular end-diastolic pressure (LVEDP) from 13.3 +/- 6.4 to 20.5 +/- 9.9 mmHg (p < 0.01) before N and from 9.7 +/- 3.2 to 12.8 +/- 5.5 mmHg after N (NS). LVEDP measured during Hg after N showed lower values than those measured before N (12.8 +/- 5.5 versus 20.5 +/- 9.9 mmHg; p < 0.01). Cardiac index (CI) increased by Hg in B (3.7 +/- 0.7 versus 4.0 +/- 1.1 L/min/m2; NS) and after N (4.5 +/- 0.7 versus 4.9 +/- 0.9 L/min/m2; NS). CI increased significantly after N at rest (3.7 +/- 0.7 versus 4.5 +/- 0.7 L/min/m2; p < 0.01) and during Hg (4.0 +/- 1.1 versus 4.9 +/- 0.9 L/min/m2; p < 0.01). The left ventricular stroke work index (LVSWI) decreased during Hg from 74.4 +/- 20.6 to 71.2 +/- 20.0 g.m/m2; NS. N caused an increase at rest to 81.4 +/- 22.5 g.m/m2; NS. LVSWI increased significantly during Hg to 83.5 +/- 26.2 g.m/m2; p < 0.05. Systemic arterial resistances (SAR) significantly decreased after N at rest (1,086.8 +/- 280.8 versus 843.5 +/- 133.1 dyne.s.cm-5; p < 0.01), but increased in B during Hg to 1,220.9 +/- 350.7 dyne.s.cm-5; p < 0.05. A significant reduction of SAR values was observed alter N during Hg (1,220.9 +/- 350.7 versus 838.9 +/- 139.9 dyne.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1990

ECoG and perilymphatic fistulae: an experimental study in the guinea pig.

Perilymph fistulae present a diagnostic dilemma to the clinician. As yet, there is no readily available, widely accepted diagnostic test. Electrocochleography (ECoG), with the advent of extratympanic recording techniques, has become a clinically applicable probe of cochlear function. Clinical ECoG was used to study guinea pigs (n = 35) both before and after surgical fistulization (n = 18) or fistulization and repair (n = 17) of the round window membrane. The animals were killed, and histopathologic examination of the temporal bones was carried out 0, 1, 3, 4, 7, 10, 14, 21, and 28 days after surgery. Of the 33 animals that survived surgery, 30 demonstrated ECoG wave-forms. No significant difference between the preoperative and postoperative wave-forms could be detected. Histopathologic study showed rapid healing of the fistulae, with no evidence of hydrops. Although there appeared to be a relatively selective loss of the outer hair cells of the cochlear basal turn, autolysis precluded detailed analysis. ECoG, as performed clinically, does not appear to detect the presence, spontaneous healing, or repair of a round window membrane fistula in the guinea pig.

Animals↗